The protocols included in this proposal are a continution of the comprehensive investigation of problems associated with cardiac transplantation which has been ongoing in this laboratory over the last 18 years. Additional protocols are proposed in the area of total heart and lung transplantation. The main areas of investigation, therefore, are: 1) basic transplantation immunology, 2) complete heart and lung transplantation, and 3) training in cardiac transplantation immunology and physiology. Experiments in transplantation immunology will include studies of the control of the recipient immune response as well as studies of the modulation of donor graft antigenicity. Studies directed toward the control of the recipient immune response will include: a) production of rabbit antithymocyte globulin (RATG) using glutaraldehyde-fixed thymus as the antigen source, b) production of RATG using other primate sources such as monkey for the antigen source (xenogeneic RATG), c) studies of potential suppressor cell stimulation by pre- and postoperative treatment of the recipient with Concanavalin A (Con A), and d) studies of total lymph node irradiation (TLI) of the recipient, with and without bone marrow transplantation, as a method for inducing tolerance. Studies of donor antigenicity modulation will include: a) pretreatment of the intact donor with drugs to decrease the recipient's immune response, and b) pretreatment of the isolated graft with drugs or radiation to decrease the recipient's immune respons. Experimental work involving total heart and lung transplantation will include: a) evaluation and correction of the breathing abnormality following heart and lung transplantation in the dog, b) studies of the relative rejection injuries in heart and lung from a common donor, c) the effect of rejection on cardiac and pulmonary physiologic parameters, and d) treatment of rejection in heart and lung transplant recipients based on rejection parameters of the heart alone.